Making accurate decisions in uncertain environments requires identifying the generative cause of sensory cues, but also the expected outcomes of possible actions. Although both cognitive processes can be formalized as Bayesian inference, they are commonly studied using different experimental frameworks, making their formal comparison difficult. Here, by framing a reversal learning task either as cue-based or outcome-based inference, we found that humans perceive the same volatile environment as more stable when inferring its hidden state by interaction with uncertain outcomes than by observation of equally uncertain cues. Multivariate patterns of magnetoencephalographic (MEG) activity reflected this behavioral difference in the neural interaction between inferred beliefs and incoming evidence, an effect originating from associative regions in the temporal lobe. Together, these findings indicate that the degree of control over the sampling of volatile environments shapes human learning and decision-making under uncertainty.The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in transcription repression and activation through binding to Gal80 repressor and Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a "fuzzy" protein interface. https://www.selleckchem.com/products/ibmx.html Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two intrinsically disordered ADs of different sequence, interact nearly identically with Med15. The finding that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts strongly with Gal80 via a distinct structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein-protein interaction.Most known porphyry Cu deposits formed in the Phanerozoic and are exclusively associated with moderately oxidized, sulfur-rich, hydrous arc-related magmas derived from partial melting of the asthenospheric mantle metasomatized by slab-derived fluids. Yet, whether similar metallogenic processes also operated in the Precambrian remains obscure. Here we address the issue by investigating the origin, fO2, and S contents of calc-alkaline plutonic rocks associated with the Haib porphyry Cu deposit in the Paleoproterozoic Richtersveld Magmatic Arc (southern Namibia), an interpreted mature island-arc setting. We show that the ca. 1886-1881 Ma ore-forming magmas, originated from a mantle-dominated source with minor crustal contributions, were relatively oxidized (1?2?log units above the fayalite-magnetite-quartz redox buffer) and sulfur-rich. These results indicate that moderately oxidized, sulfur-rich arc magma associated with porphyry Cu mineralization already existed in the late Paleoproterozoic, probably as a result of recycling of sulfate-rich seawater or sediments from the subducted oceanic lithosphere at that time.Phosphorylation of the MLKL pseudokinase by the RIPK3 kinase leads to MLKL oligomerization, translocation to, and permeabilization of, the plasma membrane to induce necroptotic cell death. The precise choreography of MLKL activation remains incompletely understood. Here, we report Monobodies, synthetic binding proteins, that bind the pseudokinase domain of MLKL within human cells and their crystal structures in complex with the human MLKL pseudokinase domain. While Monobody-32 constitutively binds the MLKL hinge region, Monobody-27 binds MLKL via an epitope that overlaps the RIPK3 binding site and is only exposed after phosphorylated MLKL disengages from RIPK3 following necroptotic stimulation. The crystal structures identified two distinct conformations of the MLKL pseudokinase domain, supporting the idea that a conformational transition accompanies MLKL disengagement from RIPK3. These studies provide further evidence that MLKL undergoes a large conformational change upon activation, and identify MLKL disengagement from RIPK3 as a key regulatory step in the necroptosis pathway.Although major advances in genomics have initiated an exciting new era of research, a lack of information regarding cis-regulatory elements has limited the genetic improvement or manipulation of pigs as a meat source and biomedical model. Here, we systematically characterize cis-regulatory elements and their functions in 12 diverse tissues from four pig breeds by adopting similar strategies as the ENCODE and Roadmap Epigenomics projects, which include RNA-seq, ATAC-seq, and ChIP-seq. In total, we generate 199 datasets and identify more than 220,000 cis-regulatory elements in the pig genome. Surprisingly, we find higher conservation of cis-regulatory elements between human and pig genomes than those between human and mouse genomes. Furthermore, the differences of topologically associating domains between the pig and human genomes are associated with morphological evolution of the head and face. Beyond generating a major new benchmark resource for pig epigenetics, our study provides basic comparative epigenetic data relevant to using pigs as models in human biomedical research.Compton scattering provides invaluable information on the underlying Fermi surface (FS) and is a powerful tool complementary to angle-resolved photoemission spectroscopy and quantum oscillation measurements. Here we perform high-resolution Compton scattering measurements for La2-xSrxCuO4 with x?=?0.08 (Tc?=?20 K) at 300 K and 150 K, and image the momentum distribution function in the two-dimensional Brillouin zone. We find that the observed images cannot be reconciled with the conventional hole-like FS believed so far. Instead, our data imply that the FS is strongly deformed by the underlying nematicity in each CuO2 plane, but the bulk FSs recover the fourfold symmetry. We also find an unusually strong temperature dependence of the momentum distribution function, which may originate from the pseudogap formation in the presence of the reconstructed FSs due to the underlying nematicity. Additional measurements for x?=?0.15 and 0.30 at 300 K suggest similar FS deformation with weaker nematicity, which nearly vanishes at x?=?0.